AS A HOSPITAL PHARMACIST, you'll see another new anti-infective, ceftazidime/avibactam (Zavicefta 2 g/0.5 g) to help combat gram-negative resistant bugs, especially AmpC, KPC, and ESBL-producing Enterobacteriaceae. We've used ceftazidime for years, but resistance can be an issue. A new beta-lactamase inhibitor, avibactam, was added to help.
Explain that adding avibactam SEEMS to lead to better coverage of resistant Enterobacteriaceae, Klebsiella, and Pseudomonas aeruginosa, BUT NOT Acinetobacter. Keep in mind that most of this evidence comes from in vitro data only. Ceftazidime/avibactam is approved for adults with complicated abdominal and urinary tract infections and seems to work as well as meropenem for abdominal infections and imipenem/cilastatin for UTIs.
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Add metronidazole empirically for abdominal infections
since ceftazidime has poor anaerobic coverage...
Give ceftazidime/avibactam 2.5 g IV every 8 hours in patients with normal renal function. Reduce the dose for patients with renal insufficiency. This can be as little as 0.94 g Q 48h for patients with CrCl < 5 mL/min. Check calculations when compounding this odd dose, 0.94 g will equal 4.5 mL. You may hear that ceftazidime/avibactam may be less effective if CrCl is between 30 to 50 mL/min, which may lead to increased mortality. BUT, let your team know this could be because the dose studied was lower than what is presently approved and few patients were studied. Let nurses know it needs to be infused over 2 hours and compatibility with other meds hasn't been established.
Expect GI and dermatologic side effects similar to ceftazidime. Don't expect ceftazidime/avibactam to replace current ceftazidime use. Put its cost in your mind. Save it for resistant abdominal infections or UTIs that are susceptible ONLY to the combo.
REFERENCES
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Lagacé-Wiens P, Walkty A, Karlowsky JA. Ceftazidime-avibactam: an evidence-based review of its pharmacology and potential use in the treatment of Gram-negative bacterial infections. Core Evid. 2014 Jan 24;9:13-25. Available at: https://www.dovepress.com/ceftazidimendashavibactam-an-evidence-based-review-of-its-pharmacology-peer-reviewed-fulltext-article-CE
Lucasti C, Popescu I, Ramesh MK, Lipka J, Sable C. Comparative study of the efficacy and safety of ceftazidime/avibactam plus metronidazole versus meropenem in the treatment of complicated intra-abdominal infections in hospitalized adults: results of a randomized, double-blind, Phase II trial. J Antimicrob Chemother. 2013 May;68(5):1183-92. Available at: https://academic.oup.com/jac/article/68/5/1183/684684
Vazquez JA, González Patzán LD, Stricklin D, Duttaroy DD, Kreidly Z, Lipka J, Sable C. Efficacy and safety of ceftazidime-avibactam versus imipenem-cilastatin in the treatment of complicated urinary tract infections, including acute pyelonephritis, in hospitalized adults: results of a prospective, investigator-blinded, randomized study. Curr Med Res Opin. 2012 Dec;28(12):1921-31. Available at: https://www.tandfonline.com/doi/abs/10.1185/03007995.2012.748653?journalCode=icmo20